Frontostriatal circuit dysfunction leads to cognitive inflexibility in neuroligin-3 R451C knockin mice.

Cognitive and behavioral rigidity are observed in various psychiatric diseases, including in autism spectrum disorder (ASD). However, the underlying mechanism remains to be elucidated. In this study, we found that neuroligin-3 (NL3) R451C knockin mouse model of autism (KI mice) exhibited deficits in behavioral flexibility in choice selection tasks. Single-unit recording of medium spiny neuron (MSN) activity in the nucleus accumbens (NAc) revealed altered encoding of decision-related cue and impaired updating of choice anticipation in KI mice. Additionally, fiber photometry demonstrated significant disruption in dynamic mesolimbic dopamine (DA) signaling for reward prediction errors (RPEs), along with reduced activity in medial prefrontal cortex (mPFC) neurons projecting to the NAc in KI mice. Interestingly, NL3 re-expression in the mPFC, but not in the NAc, rescued the deficit of flexible behaviors and simultaneously restored NAc-MSN encoding, DA dynamics, and mPFC-NAc output in KI mice. Taken together, this study reveals the frontostriatal circuit dysfunction underlying cognitive inflexibility and establishes a critical role of the mPFC NL3 deficiency in this deficit in KI mice. Therefore, these findings provide new insights into the mechanisms of cognitive and behavioral inflexibility and potential intervention strategies.

Effects of age on the time course of syntactic priming in Chinese sentence production: an ERP study.

Using a syntactic priming task, we investigated the time course of syntactic encoding in Chinese sentence production and compared encoding patterns between younger and older adults. Participants alternately read sentence descriptions and overtly described pictures, while event-related potentials (ERPs) were recorded. We manipulated the abstract prime structure (active or passive) as well as the lexical overlap of the prime and the target (verb overlap or no overlap). The syntactic choice results replicated classical abstract priming and lexical boost effects in both younger and older adults. However, when production latency was taken into account, the speed benefit from syntactic repetition differed between the two age groups. Meanwhile, preferred priming facilitated production in both age groups, whereas nonpreferred priming inhibited production in the older group. For electroencephalography, an earlier effect of syntactic repetition and a later effect of lexical overlap showed a two-stage pattern of syntactic encoding. Older adults also showed a more delayed and interactive encoding pattern than younger adults, indicating a greater reliance on lexical information. These results are illustrative of the two-stage competition and residual activation models.

Comprehensive genomic profiling of infiltrative follicular variant of papillary thyroid carcinoma.

BACKGROUND: Infiltrative follicular variant of papillary thyroid carcinoma (IFVPTC) exhibits nuclear characteristics typical of papillary thyroid carcinoma (PTC) but demonstrates a follicular growth pattern. The diagnosis of IFVPTC presenting with atypical nuclear features of PTC poses challenges for both preoperative cytopathology and postoperative histopathology. In such cases, molecular markers are needed to serve as diagnostic aids. Given the limited knowledge of IFVPTC's genomic features, this study aimed to characterize its genetic alterations and identify clinically relevant molecular markers. METHODS: Whole-exome sequencing of 50 IFVPTC tumor-normal pairs identified single-nucleotide variants, somatic copy number alterations (sCNAs), and subclonal architecture. Key mutations were verified via polymerase chain reaction and Sanger sequencing, whereas valuable biomarkers were validated via immunohistochemistry (IHC). RESULTS: This study found that endogenous processes rather than exogenous mutagens dominated the shaping of the genome of IFVPTC during tumorigenesis. BRAF V600E was the only common trunk mutation and significantly mutated gene in IFVPTC. Subcloning analysis found that most IFVPTC samples harbored two or more coexisting clones. sCNA analysis revealed that human leukocyte antigen C (HLA-C) and HLA-A were significantly amplified. Subsequent IHC investigations indicated that HLA-C shows promise in averting the misclassification of challenging-to-interpret IFVPTC and invasive encapsulated follicular variant of PTC (I-EFVPTC) as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Although there were several similarities between classic PTC and IFVPTC, they differed significantly in their sCNA patterns. CONCLUSIONS: This study provides valuable insights into IFVPTC's genetic alterations and highlights the potential of HLA-C IHC to distinguish challenging-to-interpret IFVPTC and I-EFVPTC from NIFTP, which will enhance the understanding of its molecular features for improved diagnosis and management.

Pleiotropic Effects of miR5504 Underlying Plant Height, Grain Yield and Quality in Rice.

MicroRNAs (miRNAs) are known to play critical roles in regulating rice agronomic traits through mRNA cleavage or translational repression. Our previous study indicated that miR5504 regulates plant height by affecting cell proliferation and expansion. Here, the two independent homozygous mir5504 mutants (CR1 and CR2) and overexpression lines (OE1 and OE2) were further used to investigate the functions of miR5504. The panicle length, 1000-grain weight and grain yield per plant of miR5504-OE lines were identical to those of Nipponbare (NIP), but the 1000-grain weight of mir5504 mutants was reduced by about 10% and 9%, respectively. Meanwhile, the grain width and thickness of mir5504 mutants decreased significantly by approximately 10% and 11%, respectively. Moreover, the cytological results revealed a significant decrease in cell number along grain width direction and cell width in spikelet in mir5504, compared with those in NIP. In addition, several major storage substances of the rice seeds were measured. Compared to NIP, the amylose content of the mir5504 seeds was noticeably decreased, leading to an increase of nearly 10 mm in gel consistency (GC) in mir5504 lines. Further investigation confirmed that LOC_Os08g16914 was the genuine target of miR5504: LOC_Os08g16914 over-expression plants phenocopied the mir5504 mutants. This study provides insights into the role of miR5504 in rice seed development.

Reduced expression of NUPR1 alleviates epilepsy progression via attenuating ER stress.

Epilepsy is a neurological disorder characterized by recurring seizures. It is necessary to further understand the mechanisms of epilepsy in order to develop novel strategies for its prevention and treatment. Abnormal endoplasmic reticulum stress (ERS) activation is related to the pathogenesis of epilepsy. Nuclear protein 1, transcriptional regulator (NUPR1) is involved in ERS and it might play a role in epilepsy progression. In the present study, we generated an epileptic mouse model using pilocarpine induction. After 72 h of pilocarpine treatment, the expression of NUPR1 was increased in epileptic mice. Furthermore, NUPR1 knockdown reduced the number of spontaneous recurrent seizures and alleviated hippocampal damage in these mice. Interestingly, NUPR1 knockdown also reduced the protein expression levels of LC3, PINK1, and Parkin in the mitochondria, and decreased the PINK1 expression in hippocampus. Additionally, the expression of ERS-related proteins-cleaved caspase-12, ATF4, and CHOP-decreased in epileptic mice following NUPR1 knockdown. In vitro experiments showed that the absence of NUPR1 reduced the expression of ATF4, CHOP, and cleaved caspase-12 in hippocampal neurons and inhibited the neuron apoptosis. In all, our study suggested that NUPR1 maybe a potential molecular target for epilepsy therapy.

The ETI-dependent receptor-like kinase 1 positively regulates effector-triggered immunity by stabilizing NLR-required for cell death 4 in Nicotiana benthamiana.

Leucine-rich repeat receptor-like kinases (LRR-RLKs) comprise the largest class of membrane-localized receptor-like kinases in plants. Leucine-rich repeat receptor-like kinases are key immune sectors contributing to pattern-triggered immunity (PTI), but whether LRR-RLK mediates effector-triggered immunity (ETI) in plants remains unclear. In this study, we evaluated the function of LRR-RLKs in regulating ETI by using a virus-induced gene silencing (VIGS)-based reverse genetic screening assay, and identified a LRR-RLK named ETI-dependent receptor-like kinase 1 (EDK1) required for ETI triggered by the avirulence effector AVRblb2 secreted by Phytophthora infestans and its cognate receptor Rpi-blb2. Silencing or knockout of EDK1 compromised immunity mediated by Rpi-blb2 and the cell death triggered by recognition of AVRblb2. NLR-required for cell death 4 (NRC4), a signaling component acts downstream of Rpi-blb2, was identified that interacts with EDK1 using the LC-MS analysis and the interaction was further evaluated by co-immunoprecipitation. EDK1 promotes protein accumulation of NRC4 in a kinase-dependent manner and positively regulates resistance to P. infestans in Nicotiana benthamiana. Our study revealed that EDK1 positively regulates plant ETI through modulating accumulation of the NLR signaling component NRC4, representing a new regulatory role of the membrane-localized LRR-RLKs in plant immunity.

Fluoroquinolones and the risk of severe hypoglycaemia among sulphonylurea users: Population-based cohort study.

AIM: Fluoroquinolone-related hypoglycaemia is rare but may become clinically relevant in individuals at high baseline hypoglycaemic risk, such as patients with diabetes using sulphonylureas. Our population-based cohort study assessed whether fluoroquinolones are associated with an increased risk of severe hypoglycaemia compared with amoxicillin among patients treated with sulphonylureas. MATERIALS AND METHODS: Using the UK's Clinical Practice Research Datalink Aurum linked to hospitalization and vital statistics data, we assembled a base cohort of patients who initiated second-generation sulphonylureas (1998-2020). The study cohort included patients initiating either fluoroquinolones or amoxicillin while on sulphonylureas. Using an intent-to-treat exposure definition, we assessed the 30-day risk of severe hypoglycaemia (hospitalization with or death because of hypoglycaemia) associated with fluoroquinolones compared with amoxicillin. Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of severe hypoglycaemia after 1:5 matching on previous sulphonylurea use and propensity scores. Secondary analyses were stratified by demographics and glycated haemoglobin. RESULTS: Overall, 143 417 patients initiated fluoroquinolones (n = 13 123) or amoxicillin (n = 130 294) while on sulphonylureas. Compared with amoxicillin, fluoroquinolones were not associated with the risk of severe hypoglycaemia (HR, 1.17; 95% CI, 0.91-1.50). Fluoroquinolones were associated with an increased risk in patients <65 years (HR, 2.90; 95% CI, 1.41-5.97) but not in those ≥65 years (HR, 1.03; 95% CI, 0.79-1.35) in stratified analyses. There was no evidence of effect modification by sex or glycated haemoglobin. CONCLUSIONS: In patients using second-generation sulphonylureas, fluoroquinolones were not associated with an increased risk of severe hypoglycaemia compared with amoxicillin. An increased risk among younger adults is possible.

Discriminatory fluorescence and FRET in the chiral-perovskite/RhB system.

Förster resonance energy transfer (FRET) holds a significant position in various natural and artificial systems, especially within donor-acceptor systems encompassing chiral components. Despite extensive investigations, a clear understanding of the effects of chirality and FRET on discriminatory fluorescence remains elusive. Here, chiral perovskite nanowires (CPNWs) and achiral rhodamine B (RhB) are employed to examine the FRET and discriminatory fluorescence behavior in a donor-acceptor system involving a chiral nanostructure. A notable FRET from the CPNWs to RhB is observed, along with circular dichroism (CD) and circularly polarized luminescence (CPL) activities in RhB. Although the FRET interaction remains consistent over time, a notable inversion in the polarity preference of the CD and CPL of RhB is observed. This reveals that the discriminatory fluorescence of the acceptor arises from the electromagnetic influence of the chiral donor. These findings elucidate that "chirality", as a property related to spatial orientation, cannot accompany the transfer of energy (which is a scalar) from chiral nanostructures to achiral molecules, which helps advance the understanding of the discriminatory fluorescence in the donor-acceptor system with a chiral nanostructure.

Evaluation of ChatGPT-generated medical responses: A systematic review and meta-analysis.

OBJECTIVE: Large language models (LLMs) such as ChatGPT are increasingly explored in medical domains. However, the absence of standard guidelines for performance evaluation has led to methodological inconsistencies. This study aims to summarize the available evidence on evaluating ChatGPT's performance in answering medical questions and provide direction for future research. METHODS: An extensive literature search was conducted on June 15, 2023, across ten medical databases. The keyword used was "ChatGPT," without restrictions on publication type, language, or date. Studies evaluating ChatGPT's performance in answering medical questions were included. Exclusions comprised review articles, comments, patents, non-medical evaluations of ChatGPT, and preprint studies. Data was extracted on general study characteristics, question sources, conversation processes, assessment metrics, and performance of ChatGPT. An evaluation framework for LLM in medical inquiries was proposed by integrating insights from selected literature. This study is registered with PROSPERO, CRD42023456327. RESULTS: A total of 3520 articles were identified, of which 60 were reviewed and summarized in this paper and 17 were included in the meta-analysis. ChatGPT displayed an overall integrated accuracy of 56 % (95 % CI: 51 %-60 %, I2 = 87 %) in addressing medical queries. However, the studies varied in question resource, question-asking process, and evaluation metrics. As per our proposed evaluation framework, many studies failed to report methodological details, such as the date of inquiry, version of ChatGPT, and inter-rater consistency. CONCLUSION: This review reveals ChatGPT's potential in addressing medical inquiries, but the heterogeneity of the study design and insufficient reporting might affect the results' reliability. Our proposed evaluation framework provides insights for the future study design and transparent reporting of LLM in responding to medical questions.

Effects of silencing hsa_circ_0015326 on proliferation, migration, invasion, and apoptosis of epithelial ovarian cancer cells.

Although the treatment of ovarian cancer has made great progress, there are still many patients who are not timely detected and given targeted therapy due to unknown pathogenesis. Recent studies have found that hsa_circ_0015326 is upregulated in ovarian cancer and is involved in the proliferation, invasion, and migration of ovarian cancer cells. However, whether hsa_circ_0015326 can be used as a new target of ovarian cancer needs further investigation. Therefore, the effect of hsa_circ_0015326 on epithelial ovarian cancer was investigated in this study. At first, si-hsa_circ_0015326 lentivirus was transfected into epithelial ovarian cancer cells. Then real-time fluorescence quantitative PCR (qRT-PCR) was used to detect hsa_circ_0015326 level. The proliferation of ovarian cancer cells was detected by CCK-8 assay. The horizontal and vertical migration abilities of the cells were detected by wound-healing assay and Transwell assay, respectively. Transwell assay was also used to determine the invasion rate. As for the apoptosis rate, it was assessed by flow cytometry. As a result, the expression level of hsa_circ_0015326 in A2780 and SKOV3 was found to be higher than that in IOSE-80. However, after transfecting si-hsa_circ_0015326 and si-NC into the cells, the proliferation, migration, and invasion abilities of A2780 and SKOV3 cells in the si-hsa_circ_0015326 group were significantly reduced in comparison to those in the si-NC and mock groups, while their apoptosis rates were elevated. Collectively, silencing hsa_circ_0015326 bears the capability of inhibiting the proliferation, migration, and invasion of ovarian cancer cells while increasing apoptosis rate. It can be concluded that hsa_circ_0015326 promotes the malignant biological activities of epithelial ovarian cancer cells.

Advancing the treatment of low carbon-to-nitrogen ratio municipal wastewater using a novel microaerobic sludge bed approach: Insights into enhanced performance and functional microbial community.

Microaerobic sludge bed systems could align with low-energy, reasonable carbon-nitrogen (C/N) ratio, and synchronous removal objectives during wastewater treatment. However, its ability to treat municipal wastewater (MW) with varying low C/N ratio, low NH4+ concentration, along with managing sludge bulking and loss are still unclear. Against this backdrop, this study investigated the performance of an Upflow Microaerobic Sludge Bed Reactor (UMSR) treating MW characterized by varying low C/N ratios and low NH4+ concentrations. The study also thoroughly examined associated sludge bulking and loss, pollutant removal efficiencies, sludge settleability, microbial community structures, functional gene variations, and metabolic pathways. Findings revealed that the effluent NH4+-N concentration gradually decreased to 0 mg/L with a decrease in the C/N ratio, whereas the effluent COD was unaffected by the influent, maintaining a concentration below 50 mg/L. Notably, TN removal efficiency reached 90% when C/N ratio was 3. The decrease in the C/N ratio (C/N ratio was 1) increased microbial community diversity, with abundances of AOB, AnAOB, aerobic denitrifying bacteria, and anaerobic digestion bacteria reaching 8.34%, 0.96%, 5.07%, and 9.01%, respectively. Microorganisms' metabolic pathways significantly shifted, showing increased carbohydrate and cofactor/vitamin metabolism and decreased amino acid metabolism and xenobiotic biodegradation. This study not only provides a solution for the effluent of different pre-capture carbon processes but also demonstrates the UMSR's capability in managing low C/N ratio municipal wastewater and emphasizes the critical role of microbial community adjustments and functional gene variations in enhancing nitrogen removal efficiency.

Inferences for the distribution of the duration of response in a comparative clinical study.

Duration of response is an important endpoint used in drug development. Prolonged duration for response is often viewed as an early indication of treatment efficacy. However, there are numerous difficulties in studying the distribution of duration of response based on observed data subject to right censoring in practice. The most important obstacle is that the distribution of the duration of response is in general not identifiable in the presence of censoring due to the simple fact that there is no information on the joint distribution of time to response and time to progression beyond the largest follow-up time. In this article, we introduce the restricted duration of response as a replacement of the conventional duration of response. The distribution of restricted duration of response is estimable and we have proposed several nonparametric estimators in this article. The corresponding inference procedure and additional downstream analysis have been developed. Extensive numerical simulations have been conducted to examine the finite sample performance of the proposed estimators. It appears that a new regression-based two-step estimator for the survival function of the restricted duration of response tends to have a robust and superior performance, and we recommend its use in practice. A real data example from oncology has been used to illustrate the analysis for restricted duration of response.

Cucurbitacin B modulates M2 macrophage differentiation and attenuates osteosarcoma progression via PI3K/AKT pathway.

Osteosarcoma is a common malignant bone tumour characterised by an aggressive metastatic potential. The tumour microenvironment, particularly the M2-polarised macrophages, is crucial for tumour progression. Cucurbitacin B (CuB), a triterpenoid derivative, is recognised for its anti-inflammatory and antitumour properties. This study investigates CuB and its effect on M2 macrophage differentiation and osteosarcoma progression, aiming to contribute to new treatment strategies. In vitro, THP-1 monocytes were stimulated with PMA, IL-13 and IL-4 to induce differentiation into M2 macrophages. Additionally, the influence of CuB on the proliferation, migration and invasion of osteosarcoma cells in the context of M2 macrophages was scrutinised. Crucial signalling pathways, especially the PI3K/AKT pathway, affected by CuB were identified and validated. In vivo, the osteosarcoma model was employed to gauge the effects of CuB on tumour weight, lung metastasis, angiogenesis, cell proliferation and M2 macrophage markers. The results showed that CuB inhibited M2 macrophage differentiation, leading to reduced proliferation, migration and invasion of osteosarcoma cells. CuB manifested an inhibitory effect on the PI3K/AKT pathway during the differentiation of M2 macrophages. In mouse models, CuB markedly reduced the tumour weight and the number of lung metastases. It also reduced the expression of angiogenesis and cell proliferation markers in tumour tissues, decreased the quantity of M2 macrophages and their associated markers and pathway proteins. In conclusion, CuB impedes osteosarcoma progression by inhibiting M2 macrophage differentiation via the PI3K/AKT pathway, presenting the potential for therapeutic advancements in osteosarcoma treatment.

Promotion of self-directed learning abilities among Chinese medical students through preparing for career calling and enhancing teaching competencies in medical education: a cross-sectional study.

BACKGROUND: Medical students face a heavy burden as they are tasked with acquiring a vast amount of medical knowledge within a limited time frame. Self-directed learning (SDL) has become crucial for efficient and ongoing learning among medical students. However, effective ways to foster SDL ability among Chinese medical students are lacking, and limited studies have identified factors that impact the SDL ability of medical students. This makes it challenging for educators to develop targeted strategies to improve students' SDL ability. This study aims to assess SDL ability among Chinese medical students and examine the effects of career calling and teaching competencies on SDL ability, as well as the possible mechanisms linking them. METHODS: Data were collected from 3614 respondents (effective response rate = 60.11%) using cross-sectional online questionnaires and analyzed using IBM SPSS Statistics 22.0. The questionnaire comprised a Demographic Characteristics Questionnaire, Self-directed Learning Ability Scale (Cronbach's alpha = 0.962), Teaching Competencies Scale, and Career Calling Scale. RESULTS: The average SDL ability score of Chinese medical students was 3.68 ± 0.56, indicating a moderate level of SDL ability. The six factors of the Self-directed Learning Ability Scale-self-reflection, ability to use learning methods, ability to set study plans, ability to set studying objectives, ability to adjust psychological state, and willpower in studying-accounted for 12.90%, 12.89%, 12.39%, 11.94%, 11.34%, and 8.67% of the variance, respectively. Furthermore, career calling was positively associated with SDL learning ability (ß = 0.295, p < 0.001), and SDL learning ability was positively associated with teaching competencies (ß = 0.191, p < 0.01). Simple slope analysis showed that when the level of teaching competencies was higher, the influence of career calling on SDL ability was stronger. CONCLUSIONS: Chinese medical students' SDL ability has room for improvement. Medical students could strengthen their willpower in studying by setting milestones goals with rewards, which could inspire their motivation for the next goals. Teachers should guide students to learn experience to improve students' reflective ability. Educators play a crucial role in bridging the gap between career calling education and SDL ability enhancement, highlighting the significance of optimal teaching competencies. Colleges should focus on strengthening teachers' sense of career calling and teaching competencies.

An Automatic Method for Elbow Joint Recognition, Segmentation and Reconstruction.

Elbow computerized tomography (CT) scans have been widely applied for describing elbow morphology. To enhance the objectivity and efficiency of clinical diagnosis, an automatic method to recognize, segment, and reconstruct elbow joint bones is proposed in this study. The method involves three steps: initially, the humerus, ulna, and radius are automatically recognized based on the anatomical features of the elbow joint, and the prompt boxes are generated. Subsequently, elbow MedSAM is obtained through transfer learning, which accurately segments the CT images by integrating the prompt boxes. After that, hole-filling and object reclassification steps are executed to refine the mask. Finally, three-dimensional (3D) reconstruction is conducted seamlessly using the marching cube algorithm. To validate the reliability and accuracy of the method, the images were compared to the masks labeled by senior surgeons. Quantitative evaluation of segmentation results revealed median intersection over union (IoU) values of 0.963, 0.959, and 0.950 for the humerus, ulna, and radius, respectively. Additionally, the reconstructed surface errors were measured at 1.127, 1.523, and 2.062 mm, respectively. Consequently, the automatic elbow reconstruction method demonstrates promising capabilities in clinical diagnosis, preoperative planning, and intraoperative navigation for elbow joint diseases.

Exploration of the Dynamic Variations of the Characteristic Constituents and the Degradation Products of Catalpol during the Process of Radix Rehmanniae.

Radix Rehmanniae (RR), a famous traditional Chinese medicine (TCM) widely employed in nourishing Yin and invigorating the kidney, has three common processing forms in clinical practice, including fresh Radix Rehmanniae (FRR), raw Radix Rehmanniae (RRR), and processed Radix Rehmanniae (PRR). However, until now, there has been less exploration of the dynamic variations in the characteristic constituents and degradation products of catalpol as a representative iridoid glycoside with the highest content in RR during the process from FRR to PRR. In this study, an ultra-performance liquid chromatography coupled with photodiode array detector (UPLC-PDA) method was successfully established for the simultaneous determination of ten characteristic components to explore their dynamic variations in different processed products of RR. Among them, iridoid glycosides, especially catalpol, exhibited a sharp decrease from RRR to PRR. Then, three degradation products of catalpol were detected under simulated processing conditions (100 °C, pH 4.8 acetate buffer solution), which were isolated and identified as jiofuraldehyde, cataldehyde, and norviburtinal, respectively. Cataldehyde was first reported as a new compound. Moreover, the specificity of norviburtinal in self-made PRR samples was discovered and validated, which was further confirmed by testing in commercially available PRR samples. In conclusion, our study revealed the decrease in iridoid glycosides and the production of new degradation substances during the process from FRR to PRR, which is critical for unveiling the processing mechanism of RR.

Covalent and non-covalent interaction of myofibrillar protein and cyanidin-3-O-glucoside: focus on structure, binding sites and in vitro digestion properties.

BACKGROUND: The aim of this study was to investigate the effects of covalent and non-covalent interactions between myofibrillar protein (MP) and cyanidin-3-O-glucoside (C3G) on protein structure, binding sites, and digestion properties. Four methods of inducing covalent cross-linking were used in the preparation of MP-C3G conjugates, including tyrosinase-catalyzed oxidation, alkaline pH shift treatment, free radical grafting, and ultrasonic treatment. A comparison was made between MP-C3G conjugates and complexes, and the analysis included sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), C3G binding ratio, liquid chromatography-tandem mass spectrometry (LC-MS/MS), protein side-chain amino acids, circular dichroism spectroscopy, three-dimensional fluorescence, particle size, and in vitro simulated digestion. RESULTS: Covalent bonding between C3G and amino acid side chains in MP was confirmed by LC-MS/MS. In covalent bonding, tryptophan residues, free amino groups and sulfhydryl groups were all implicated. Among the 22 peptides covalently modified by C3G, 30 modification sites were identified, located in lysine, histidine, tryptophan, arginine and cysteine. In vitro simulated digestion experiments showed that the addition of C3G significantly reduced the digestibility of MP, with the covalent conjugate showing lower digestibility than the non-covalent conjugate. Moreover, the digestibility of protein decreased more during intestinal digestion, possibly because covalent cross-linking of C3G and MP further inhibited trypsin targeting sites (lysine and arginine). CONCLUSION: Covalent cross-linking of C3G with myofibrillar proteins significantly affected protein structure and reduced protein digestibility by occupying more trypsin binding sites. © 2023 Society of Chemical Industry.

Changes in chemical components and hepatoprotective effect of red Panax notoginseng processed by aspartic acid impregnation treatment.

BACKGROUND: Red Panax notoginseng (RPN) is one of the major processed products of P. notoginseng (PN), with more effective biological activities. However, the traditional processing method of RPN has some disadvantages, such as low conversion rate of ginsenosides and long processing time. RESULTS: In this work, we developed a green, safe, and efficient approach for RPN processing by aspartic acid impregnation pretreatment. Our results showed that the optimized temperature, steaming time, and concentration of aspartic acid were 120 °C, 1 h, and 3% respectively. The original ginsenosides in PN treated by aspartic acid (Asp-PN) were completely converted to rare saponins at 120 °C within just 1 h. The concentration of the rare ginsenosides in Asp-PN was two times higher than that in untreated RPN. In addition, we examined the protective effect of RPN and Asp-PN on acetaminophen-induced liver injury in a mouse model. The results showed that Asp-PN has significantly more potent hepatoprotective action than the RPN. The hepatoprotection of Asp-PN in acetaminophen-induced hepatotoxicity may be due to its anti-oxidative stress, anti-apoptotic, and anti-inflammatory activities. CONCLUSION: These results indicated that aspartic acid impregnation pretreatment may provide an effective method to shorten the steaming time, improve the conversion rate of ginsenosides, and enhance hepatoprotective activity of RPN. © 2024 Society of Chemical Industry.

Vertebral Artery Stenting for Acute Multiple Cerebral Infarctions Caused by Vertebral Artery Dissection After Massage: A Case Report.

Vertebral artery dissection is a rare pathology that can cause ischemic stroke in young people. Cervical massage, especially improper pulling manipulation, is a cause of vertebral artery dissection. We present a case of 32-year-old woman who developed acute multiple posterior circulation ischemic cerebral infarctions as a result of left vertebral artery V4 segment dissection after receiving neck massage. She underwent emergency vertebral artery stent implantation at the site of the dissection. Symptoms were relieved the day after treatment. The patient recovered without adverse complications or endovascular restenosis in the following year.

[Isolation and identification of malonyl ginsenoside-Ra_1 and malonyl ginsenoside-Ra_2 from fresh roots of Panax ginseng].

The aim of this paper is to study the malonyl ginsenosides in the fresh roots of Panax ginseng. D101 macroporous adsorption resin, ODS, and preparative HPLC were employed to separate the chemical components from the 70% ethanol extract of the fresh roots of P. ginseng, and the structures of the separated compounds were identified based on the data of high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Two malonyl ginsenosides were isolated from the fresh roots of P. ginseng and identified as 3-O-\[6-O-malonyl-ß-D-glucopyranosyl-(1→2)-ß-D-glucopyranosyl\]-20-O-\[ ß-D-xylopyranosyl-(1→4)-α-L-arabinopyranosyl-(1→6)-ß-D-glucopyranosyl\]-dammar-24-ene-3ß,12ß,20S-triol(1) and 3-O-\[6-O-malonyl-ß-D-glucopyranosyl-(1→2)-ß-D-glucopyranosyl\]-20-O-\[ ß-D-xylopyranosyl-(1→2)-α-L-arabinofuranosyl-(1→6)-ß-D-glucopyranosyl\]-dammar-24-ene-3ß,12ß,20S-triol(2), respectively. Compounds 1 and 2 are new compounds isolated from fresh roots of P. ginseng for the first time and named as malonyl ginsenoside-Ra_1 and malonyl ginsenoside-Ra_2, respectively.